Normal cells from humans and from several other species of animals are limited in the number of doublings they can achieve in culture (i,e., they have a finite in vitro life-span). We wish to try to understand the processes which lead to the eventual cessation of growth of these normal cell cultures. To this end we will employ well known cell hybridization techniques in a way which has not yet been applied to studies of in vitro cellular aging. Proliferating hybrid cell populations will be obtained from the fusion of clones each with a different doubling potential. Mutant human diploid fibroblasts will be used as one fusion parent to allow biochemical selection of the hybrid cells. For these experiments we will fuse: 1) two normal human diploid clones with varying proliferative potential; 2) normal human clones with clones from human cell lines with infinite proliferative potential; and 3) normal human clones with clones from other normal animal cell cultures. Comparison of the division potential of the hybrids with the division potential of the parental cell populations will give us important insight into the processes which limit normal cell proliferation.